Oral Vitamin C Reduced Death Risk in Phase 2 Trial of Pre-Leukemia Conditions
A phase 2 trial evaluated daily vitamin C in patients with clonal cytopenia and lower-risk myeloid malignancies.
Researchers from the University of Copenhagen and the Van Andel Institute evaluated oral vitamin C in patients with pre-leukemic conditions and early-stage blood disorders. The findings from the multicenter, randomized EVITA clinical trial were published in Cancer wiley.com
Cancerwiley.comOpen source ↗. The trial enrolled 109 adult participants in Denmark and the United States between November 1, 2017, and September 28, 2022.
Participants had diagnoses of clonal cytopenia of undetermined significance (CCUS) or lower-risk myeloid malignancies without concurrent anticancer therapy. The cohort was randomized into two arms: 55 individuals received 1000 mg of oral vitamin C daily for 12 months, while 54 received a placebo. Vitamin C acts as a cofactor for TET enzymes involved in DNA demethylation and epigenetic regulation, which are frequently altered by TET2 mutations in leukemia drivers.
Primary End Point and Clonal Growth
The primary outcome assessed in EVITA was the median clonal growth rate from baseline to the conclusion of the 12-month intervention. Authors reported that this primary end point did not differ between the treatment and control arms. Despite the lack of divergence in clonal growth rates, secondary measures showed biological activity, including changes in inflammatory cytokine trajectories between cohorts.
Additionally, five participants in the vitamin C cohort developed higher-risk hematologic malignancies compared to nine individuals in the placebo cohort wiley.com
Cancerwiley.comOpen source ↗. The trial also demonstrated that supplementation normalized vitamin C concentrations in individuals who exhibited baseline deficiencies.
Safety Profile and Survival Metrics
Safety assessments revealed fewer serious adverse events in the active intervention cohort. Serious adverse events occurred in 18 of 55 participants (33%) receiving vitamin C, compared to 30 of 53 participants (57%) in the placebo arm.
In exploratory analyses across follow-up, overall survival was longer in the vitamin C group, showing a hazard ratio of 0.35. Over three years of follow-up, this corresponded to a 65 percent lower risk of death in the treated group. The investigators stated that a phase 3 trial is warranted to confirm clinical efficacy.
